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1.
Soft Matter ; 20(1): 212-223, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38078477

ABSTRACT

Extensibility is beyond the paradigm of classical soft glassy materials, and more broadly, yield-stress fluids. Recently, model yield-stress fluids with significant extensibility have been designed by adding polymeric phases to classically viscoplastic dispersions [Nelson et al., J. Rheol., 2018, 62, 357; Nelson et al., Curr. Opin. Solid State Mater. Sci., 2019, 23, 100758; Dekker et al., J. Non-Newtonian Fluid Mech., 2022, 310, 104938]. However, fundamental questions remain about the design of and coupling between the shear and extensional rheology of such systems. In this work, we propose a model material, a mixture of soft glassy microgels and solutions of high molecular weight linear polymers. We establish systematic criteria for the design and thorough rheological characterization of such systems, in both shear and extension. Using our material, we show that it is possible to dramatically change the behavior in extension with minimal change in the shear yield stress and elastic modulus, thus enabling applications that exploit orthogonal modulation of shear and extensional material properties.

2.
An Acad Bras Cienc ; 95(suppl 2): e20230519, 2023.
Article in English | MEDLINE | ID: mdl-38126525

ABSTRACT

Monogeneans are a diverse group of flatworms, being ectoparasites of marine and freshwater fish, with great morphological and ecological variety. Analyzes of monogenetics in fish with great habitat diversity such as snappers are scarce in the literature, which already emphasizes the need for an update in this regard. The presente study found, morphologically characterized and mapped the geographic distribution and in known hosts the species Microcotyloides incisa and Microcotyloides impudicus, describing the first occurrence of these monogeneans for South America and in new hosts. The survey of hosts in the literature shows that M. incisa seems to have a greater Affinity with congener species of Lutjanidae and fish from other families, which may indicate a preference or specificity for fish of this family because they are congeners of their host type. The introduction of these parasites into South American waters may have occurred due to the migratory behavior of snappers, which are well distributed along the Mexican coast, where the parasites are usually reported. Here, we also bring the first occurrence of M. incisa for Lutjanus analis and Lutjanus jocu and M. impudicus for Ocyurus chrysurus and Lutjanus synagris, helping in the mapping and distribution of these monogenetic species in the Americas.


Subject(s)
Fish Diseases , Parasites , Perciformes , Platyhelminths , Trematoda , Humans , Animals , Brazil , Fishes , Perciformes/parasitology , Fish Diseases/parasitology
3.
Anim Genet ; 54(3): 375-388, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36756733

ABSTRACT

Computer vision system (CVSs) are effective tools that enable large-scale phenotyping with a low-cost and non-invasive method, which avoids animal stress. Economically important traits, such as rib and loin yield, are difficult to measure; therefore, the use of CVS is crucial to accurately predict several measures to allow their inclusion in breeding goals by indirect predictors. Therefore, this study aimed (1) to validate CVS by a deep learning approach and to automatically predict morphometric measurements in tambaqui and (2) to estimate genetic parameters for growth traits and body yield. Data from 365 individuals belonging to 11 full-sib families were evaluated. Seven growth traits were measured. After biometrics, each fish was processed in the following body regions: head, rib, loin, R + L (rib + loin). For deep learning image segmentation, we adopted a method based on the instance segmentation of the Mask R-CNN (Region-based Convolutional Neural Networks) model. Pearson's correlation values between measurements predicted manually and automatically by the CVS were high and positive. Regarding the classification performance, visible differences were detected in only about 3% of the images. Heritability estimates for growth and body yield traits ranged from low to high. The genetic correlations between the percentage of body parts and morphometric characteristics were favorable and highly correlated, except for percentage head, whose correlations were unfavorable. In conclusion, the CVS validated in this image dataset proved to be resilient and can be used for large-scale phenotyping in tambaqui. The weight of the rib and loin are traits under moderate genetic control and should respond to selection. In addition, standard length and pelvis length can be used as an efficient and indirect selection criterion for body yield in this tambaqui population.


Subject(s)
Characiformes , Deep Learning , Animals , Artificial Intelligence , Body Weights and Measures , Ribs
4.
Preprint in English | medRxiv | ID: ppmedrxiv-22273608

ABSTRACT

BackgroundThe coronavirus disease 2019 (COVID-19) is a widespread, highly contagious inflammatory process that causes respiratory, physical and psychological dysfunction. COVID-19 mainly affects the respiratory system and evolves in the acute phase from mild cases with common symptoms, such as fever, cough, and fatigue, to the moderate-to-severe form, causing massive alveolar damage resulting in dyspnea and hypoxemia that can rapidly progress to pneumonia, and acute respiratory distress syndrome. The acute form usually causes severe pulmonary sequelae such as pulmonary fibrosis or progression to organ failure, leading to worsening metabolic dysfunction and/or death. PurposeTo verify the effects of an outpatient and home pulmonary rehabilitation program (PRP) on clinical symptoms, pulmonary function, physical activity level, functional status, autonomic activity, peripheral muscle strength, static and functional balance, functional mobility, anxiety and depression, post-traumatic stress, health-related quality of life, and survival of patients with sequelae from COVID-19. MethodsThis study will be a cohort, parallel, two-arm multicentric study, to be carried out in three clinical centers, with blind evaluation, with 06 weeks of training and follow-up. This study was designed according to the recommendations of the CONSORT statement. To be involved in this clinical study, according to the inclusion criteria, women and men aged between 16 and 75 years affected by COVID-19. The proposed PRP is based on the guidelines recommended by the Global Initiative for Chronic Obstructive Lung Disease and, consists of a combination of aerobic and muscle strengthening exercises, lasting six weeks, with a frequency of three times a week. DiscussionIn patients infected with COVID-19 with persistent symptoms and sequelae, PRP mainly seeks to improve dyspnea, relieve anxiety and depression, prevent, and reduce complications and/or dysfunctions, reduce morbidity and mortality, and improve health-related quality of life. Trial registrationThis study was registered at clinicaltrials.gov (ID: COVID-19 PULMONARY REHAB NCT04982042).

5.
Acta Trop ; 210: 105577, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32526168

ABSTRACT

Shelters are places that receive certain species of domestic animals, mostly dogs and cats, that are normally abandoned. These animals are easy to handle because they are crowded and have limited movement. Dogs, due to the close relationship with humans, are considered the main domestic reservoirs in the peridomiciliary cycle of American trypanosomiasis infection in humans. Therefore, in several countries studies are carried out to assess the occurrence of infection in these animals. This work evaluated the occurrence of Trypanosoma cruzi in dogs from shelters in the city of Aracaju, Sergipe. This was an observational and cross-sectional study to detect the occurrence of T. cruzi in blood samples from shelter dogs using polymerase chain reaction (PCR) with the TcZ1/TcZ2 primers. A total of 168 blood samples from dogs (104 females and 64 males) were collected and subjected to DNA and PCR extraction, and seventeen (10.1%) samples showed amplification of the product of the expected size. The TcZ1/TcZ2 primer pair used is considered specific for T. cruzi, and it is capable of amplifying all strains without amplifying other Trypanosoma species. The shelters evaluated had different physical infrastructure; animals positive for T. cruzi were found in all of them, as confirmed by sequencing. It is concluded that shelter dogs, as well as other domestic animals, can function as indicators of the occurrence of T. cruzi in Aracaju-SE, providing relevant epidemiological information for health surveillance and monitoring of Trypanosomatid infections.


Subject(s)
Chagas Disease/transmission , Disease Reservoirs/parasitology , Dogs/parasitology , Trypanosoma cruzi/isolation & purification , Animals , Brazil/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Polymerase Chain Reaction/veterinary , Trypanosoma cruzi/genetics
6.
An Acad Bras Cienc ; 91(4): e20190544, 2019.
Article in English | MEDLINE | ID: mdl-31800710

ABSTRACT

Lutjanids are marine fish and commonly inhabit coral reefs, which have migratory habits and feed in a general way, due to these characteristics, are susceptible to infections by parasites, such as cuculanid nematodes. This work aimed to report for the first time, the occurrence of Dichelyne (Dichelyne) bonacii in Brazil, in two new hosts, Lutjanus analis and Rhomboplites aurorubens, acquired from local artisanal fishermen at the Aracaju city public fishing terminal (10 ° 54'17 "S37 ° 2'56" W), northeast coast of Brazil. Adult nematodes were collected from the intestinal tract of the hosts, clarified in Aman's Lactophenol and were briefly described here. Three adult males and five gravid females were found, indicating that the two species of fish acted as definitive hosts. Currently, this species of parasite has been reported only from fish collected in the coast of Mexico, which makes this work the first record of this parasite in Brazilian coastal waters. The results show that probably the range of hosts and the distribution of D. (Dichelyne) bonacii is not as restricted as data pointed in the literature, being a little wider, extending also to waters that bathe the Brazilian coast.


Subject(s)
Fish Diseases/parasitology , Nematoda/anatomy & histology , Nematoda/classification , Perciformes/parasitology , Animals , Brazil , Female , Male , Nematoda/isolation & purification
7.
J Parasitol Res ; 2019: 8176283, 2019.
Article in English | MEDLINE | ID: mdl-31186949

ABSTRACT

Parasitic isopod species are poorly known in the northeastern coast of Brazil. In this sense, this study presents novel records of Isopoda of the families Aegidae, Cymothoidae, and Corallanidae. A total 69 specimens of Lutjanus analis and 19 of Lutjanus jocu, of which 46 isopods from 3 different species were collected, i.e. Rocinela signata, Cymothoa excisa, and Excorallana richardsoni. The species R. siganata and E. richardsoni are reported for the first time in L. jocu. A significant relationship between the parasite R. signata and the size of the fish L. jocu was also observed. The isopod C. excisa is considered an incidental finding in L. analis. To the authors' knowledge, this is the first report of this species in fish from Brazil. The three species of isopods are new occurrences in the State of Sergipe, northeast region of the country. An additional morphological characteristic observed in the dorsal setae of pleotelson in specimens of E. richardsoni was that one end of this structure wws bifid. This information contributes to the current body of knowledge of the morphology of this particular species.

8.
Can J Infect Dis Med Microbiol ; 2018: 7020541, 2018.
Article in English | MEDLINE | ID: mdl-30364104

ABSTRACT

Updated information of the dispersion dynamics of Chagas disease (CD) and a systemic analysis of these data will aid the early identification of areas that are vulnerable to transmission and enable efficient intervention. This work synthesized spatiotemporal information regarding triatomine fauna and analyzed this information in combination with the results from serological tests to elucidate the epidemiological panorama of CD in the state of Sergipe, Brazil. This is a retrospective analytical study that utilized information from the database of the National Chagas Disease Control Program. Between 2010 and 2016, 838 triatomines of eight species, namely, Panstrongylus geniculatus, which was first recorded in the state of Sergipe, Panstrongylus lutzi, P. megistus, Triatoma brasiliensis, T. pseudomaculata, T. tibiamaculata, T. melanocephala, and Rhodnius neglectus, were collected. Optical microscopy revealed that 13.2% of triatomines examined were infected by Trypanosoma cruzi-like flagellates. The distribution of triatomines exhibits an expanding south-central to northern dispersion, with a preference for semiarid and agreste areas and occasional observations in humid coastal areas due to anthropogenic actions reflected in the environment. Of the human cases analyzed from 2012 to 2016, 8.3% (191/2316) presented positive serology for Trypanosoma cruzi, and this proportion showed a gradual increase in the southern center of the state and new notifications in coastal regions. There is a need for intensification and continuity of the measures adopted by the Chagas Disease Control Program in Sergipe, identifying new priority areas for intervention and preferential ecotopes of the vectors, considering the occurrence of positive triatomines intradomicilliary and a source of new triatomines in the peridomiciles.

9.
Magn Reson Chem ; 56(5): 321-328, 2018 05.
Article in English | MEDLINE | ID: mdl-29327368

ABSTRACT

Mechanical compression of polymer gels provides a simple way for the measurement of residual chemical shift anisotropies, which then can be employed, on its own, or in combination with residual dipolar couplings, for structural elucidation purposes. Residual chemical shift anisotropies measured using compression devices needed a posteriori correction to account for the increase of the polymer to solvent ratio inside the swollen gel. This correction has been cast before in terms of a single-free parameter which, as shown here, can be simultaneously optimized along with the components of the alignment tensor while still retaining discriminating power of the different relative configurations as illustrated in the stereochemical analysis of α-santonin and 10-epi-8-deoxycumambrin B.


Subject(s)
Carbon Isotopes/chemistry , Gels/chemistry , Polymethyl Methacrylate/chemistry , Anisotropy , Carbon-13 Magnetic Resonance Spectroscopy/methods , Compressive Strength , Models, Molecular , Molecular Conformation , Santonin/chemistry , Sesquiterpenes/chemistry , Solvents/chemistry , Stereoisomerism , Thermodynamics
10.
An Acad Bras Cienc ; 89(3 Suppl): 2281-2291, 2017.
Article in English | MEDLINE | ID: mdl-28746553

ABSTRACT

Parasites are important components of communities and constitute great part of the biological diversity found in ecosystems, providing valuable information about their hosts and the environment in which they live. However, despite its importance, parasitic diversity is still not well known in some regions of Brazil, especially with respect to fish parasites in the Northeast Region. The present study aims to perform the survey of gill parasites of fish from two tropical estuaries located in northeastern Brazil: Paraíba and Mamanguape rivers. Two collections were made in each estuary, one during the dry period (November / 2013) and the other during the rainy season (July / 2014). The fish were caught using a beach seine net, dragged along the main channel margin. After the identification, biometry and necropsy of the fish, their parasites were collected, stored and identified. For each species of parasite, the values ​​of prevalence, mean intensity and mean abundance were calculated. Of the 882 examined fish, belonging to four species, 145 were parasitized by at least one species of parasite. In total, 18 taxa of parasites of the groups Monogenea, Digenea, Nematoda, Copepoda and Isopoda were recorded, being the copepod Acusicola brasiliensis the most abundant species of parasite.


Subject(s)
Biodiversity , Fishes/parasitology , Gills/parasitology , Invertebrates/classification , Animals , Brazil , Estuaries , Fishes/classification , Seasons
11.
An. acad. bras. ciênc ; 89(3,supl): 2281-2291, 2017. tab, graf
Article in English | LILACS | ID: biblio-886822

ABSTRACT

ABSTRACT Parasites are important components of communities and constitute great part of the biological diversity found in ecosystems, providing valuable information about their hosts and the environment in which they live. However, despite its importance, parasitic diversity is still not well known in some regions of Brazil, especially with respect to fish parasites in the Northeast Region. The present study aims to perform the survey of gill parasites of fish from two tropical estuaries located in northeastern Brazil: Paraíba and Mamanguape rivers. Two collections were made in each estuary, one during the dry period (November / 2013) and the other during the rainy season (July / 2014). The fish were caught using a beach seine net, dragged along the main channel margin. After the identification, biometry and necropsy of the fish, their parasites were collected, stored and identified. For each species of parasite, the values ​​of prevalence, mean intensity and mean abundance were calculated. Of the 882 examined fish, belonging to four species, 145 were parasitized by at least one species of parasite. In total, 18 taxa of parasites of the groups Monogenea, Digenea, Nematoda, Copepoda and Isopoda were recorded, being the copepod Acusicola brasiliensis the most abundant species of parasite.


Subject(s)
Animals , Biodiversity , Fishes/parasitology , Gills/parasitology , Invertebrates/classification , Seasons , Brazil , Estuaries , Fishes/classification
12.
Chemistry ; 22(46): 16632-16635, 2016 Nov 07.
Article in English | MEDLINE | ID: mdl-27739109

ABSTRACT

Anisotropic NMR parameters, such as residual dipolar couplings (RDCs), residual chemical shift anisotropies (RCSAs) and residual quadrupolar couplings (RQCs or ΔνQ ), appear in solution-state NMR when the molecules under study are subjected to a degree of order. The tunable alignment by reversible compression/relaxation of gels (PMMA and p-HEMA) is an easy, user-friendly, and very affordable method to measure them. When using this method, a fraction of isotropic NMR signals is observed in the NMR spectra, even at a maximum degree of compression. To explain the origin of these isotropic signals we decided to investigate their physical location inside the NMR tube using deuterium 1D imaging and MRI micro-imaging experiments. It was observed that after a certain degree of compression the gels start to buckle and they generate pockets of isotropic solvent, which are never eliminated. The amount of buckling depends on the amount of cross-linker and the length of the gel.

13.
Quintessence Int ; 46(10): 863-70, 2015.
Article in English | MEDLINE | ID: mdl-26345101

ABSTRACT

OBJECTIVE: The aim of this study was to compare the use of periodontal probing and cone beam computed tomography (CBCT) images in the diagnosis of furcation involvement (FI) in patients with chronic generalized severe periodontitis. METHOD AND MATERIALS: Fifteen patients with chronic generalized severe periodontitis were included in this study. In total, 174 furcation sites (all in molar teeth) were analyzed. FI was assessed at three sites (buccal, mesiopalatal, and distopalatal) of maxillary molars, and at two sites (buccal and oral) of mandibular molars. FI was assessed both clinically (periodontal probing) and on CBCT images, using a dichotomous scale (present/absent). The agreement between clinical and CBCT-based findings was calculated. RESULTS: FI were more often detected by means of CBCT than by means of clinical examination. Agreement between the evaluation methods was present in 46.9% of cases (63.3% in maxilla, 45.0% in mandible). FI detected clinically was confirmed by means of CBCT in 24% of the evaluated sites. The largest agreement (73.7%) in FI detection was found in the distopalatal maxillary sites between CBCT and clinical probing. The smallest agreement (36.6%) was found in the buccal sites of the mandibular molars, in which 63.3% of FI were detected using CBCT only, but not clinically. CONCLUSION: The number of FI detected by means of CBCT was larger than by means of periodontal probing. In those cases in which chronic generalized severe periodontitis is clinically diagnosed, and surgical treatment is necessary, CBCT may be suggested as an adjunct tool for FI assessment.


Subject(s)
Chronic Periodontitis/complications , Chronic Periodontitis/diagnostic imaging , Cone-Beam Computed Tomography , Furcation Defects/diagnostic imaging , Furcation Defects/etiology , Adult , Chronic Periodontitis/therapy , Female , Humans , Male , Middle Aged , Molar , Periodontal Index
14.
Eur J Pharm Sci ; 38(5): 548-55, 2009 Dec 08.
Article in English | MEDLINE | ID: mdl-19833200

ABSTRACT

In the last decades, the incidence of histoplasmosis, a pulmonary fungal disease caused by Histoplasma capsulatum, has increased worldwide. In this context, vaccines for the prevention of this infection or therapies are necessary. Cell-free antigens (CFAgs) from H. capsulatum when administered for murine immunization purposes are able to confer protection and control of the infection, since they activate cellular immunity. However, the most of vaccination procedures need several antigens administrations and immunoadjuvants, which are not approved for use in humans. The aim of this study was to develop and characterize a vaccination approach using biodegradable PLGA microspheres (MS) that could allow the controlled and/or sustained release of the encapsulated antigens from H. capsulatum. CFAgs-loaded MS presented a size less than 10 microm, were marked engulfed by bone marrow-derived macrophages (BMDM phi) and induced the nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production by these cells. Our data show that CFAgs-loaded MS induce cell activation, suggesting an immunostimulant effect to be further investigated during immunization procedures. CFAgs-loaded MS present potential to be used as vaccine in order to confer protection against H. capsulatum infection.


Subject(s)
Antigens, Fungal/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacokinetics , Histoplasma/chemistry , Histoplasma/immunology , Microspheres , Animals , Antigens, Fungal/metabolism , Cells, Cultured , Histoplasma/metabolism , Mice , Subcellular Fractions/chemistry , Subcellular Fractions/metabolism
15.
J Immune Based Ther Vaccines ; 7: 4, 2009 Sep 15.
Article in English | MEDLINE | ID: mdl-19754943

ABSTRACT

BACKGROUND: Our group previously demonstrated that a DNA plasmid encoding the mycobacterial 65-kDa heat shock protein (DNA-HSP65) displayed prophylactic and therapeutic effect in a mice model for tuberculosis. This protection was attributed to induction of a strong cellular immunity against HSP65. As specific immunity to HSP60 family has been detected in arthritis, multiple sclerosis and diabetes, the vaccination procedure with DNA-HSP65 could induce a cross-reactive immune response that could trigger or worsen these autoimmune diseases. METHODS: In this investigation was evaluated the effect of a previous vaccination with DNA-HSP65 on diabetes development induced by Streptozotocin (STZ). C57BL/6 mice received three vaccine doses or the corresponding empty vector and were then injected with multiple low doses of STZ. RESULTS: DNA-HSP65 vaccination protected mice from STZ induced insulitis and this was associated with higher production of IL-10 in spleen and also in the islets. This protective effect was also concomitant with the appearance of a regulatory cell population in the spleen and a decreased infiltration of the islets by T CD8+ lymphocytes. The vector (DNAv) also determined immunomodulation but its protective effect against insulitis was very discrete. CONCLUSION: The data presented in this study encourages a further investigation in the regulatory potential of the DNA-HSP65 construct. Our findings have important implications for the development of new immune therapy strategies to combat autoimmune diseases.

16.
Expert Rev Vaccines ; 8(2): 239-52, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19196203

ABSTRACT

Vaccination is one of the most powerful health tools available owing to its ability to confer protection against various diseases. The long-term impact of such protection in terms of public-health savings is nearly incalculable and becomes even more evident when considering if the vaccination concept is extended to the therapeutic potential of a given molecule. In this sense, DNA vaccines are especially important tools with enormous potential owing to the molecular precision that they offer. The properties of the plasmid DNA molecule in terms of stability, cost-effectiveness and lack of cold-chain requirement are additional advantages over traditional vaccines and therapeutics. We focus on the current knowledge of autoimmune mechanisms, engineering of DNA vaccines and attempts that have already been made in order to intervene in autoimmune processes. Our experience with a genetic vaccine containing the heat-shock protein gene (hsp65) from mycobacteria is also described.


Subject(s)
Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , Vaccines, DNA/immunology , Vaccines, DNA/therapeutic use , Bacterial Proteins/genetics , Bacterial Proteins/immunology , Chaperonin 60 , Chaperonins/genetics , Chaperonins/immunology , Humans
17.
Acta Clin Belg ; 63(4): 219-20, 2008.
Article in English | MEDLINE | ID: mdl-19048697
18.
Eur Psychiatry ; 22(3): 137-41, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17188846

ABSTRACT

AIM: The Belgian medical world has acknowledged the diagnosis of transsexualism and accepted Sex Reassignment Surgery (SRS) as one of the steps in the treatment of choice since 1985. This prevalence and demographic study analyses data on all Belgian individuals who have undergone SRS since that year. METHODS: All (188) plastic surgeons as well as all gender teams (Antwerp, Bruges, Ghent, and Liège) in Belgium were sent demographic questionnaires to be completed for each of their transsexual patients. RESULTS: The results show an overall prevalence of 1:12,900 for male-to-female and 1:33,800 for female-to-male transsexuals in Belgium. In Wallonia (the French-speaking region of Belgium) the prevalence is significantly lower than in Flanders (the Dutch-speaking region) and in Brussels (the bilingual capital region). In the total Belgian population the male/female sex ratio is 2.43:1, again with a substantial difference between Wallonia on the one hand and Flanders on the other. DISCUSSION AND CONCLUSION: While in Flanders and in Brussels the prevalence is comparable to that in other Western European countries, in Wallonia it is markedly lower. Transsexualism in Wallonia appears to be socially less acceptable: persons suffering from gender dysphoria in that part of Belgium encounter more problems accessing gender clinics and receiving treatment.


Subject(s)
Demography , Transsexualism/epidemiology , Adolescent , Adult , Aged , Belgium , Cross-Sectional Studies , Female , Genitalia, Female/surgery , Genitalia, Male/surgery , Health Services Accessibility/statistics & numerical data , Humans , Male , Middle Aged , Patient Care Team , Sex Ratio , Socioeconomic Factors , Surgery, Plastic/statistics & numerical data , Surveys and Questionnaires , Topography, Medical , Transsexualism/diagnosis , Transsexualism/surgery
19.
Hum Gene Ther ; 16(11): 1338-45, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16259568

ABSTRACT

We described a prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65-kDa heat shock protein (DNA-hsp65) in experimental murine tuberculosis. However, high homology of the vaccine to the corresponding mammalian hsp60, together with the CpG motifs in the plasmidial vector, could trigger or exacerbate an autoimmune disease. In the present study, we evaluate the potential of DNA-hsp65 vaccination to induce or modulate arthritis in mice genetically selected for acute inflammatory reaction (AIR), either maximal (AIRmax) or minimal (AIRmin). Mice immunized with DNA-hsp65 or injected with the corresponding DNA vector (DNAv) developed no arthritis, whereas pristane injection resulted in arthritis in 62% of AIRmax mice and 7.3% of AIRmin mice. Administered after pristane, DNA-hsp65 downregulated arthritis induction in AIRmax animals. Levels of interleukin (IL)-12 were significantly lower in mice receiving pristane plus DNA-hsp65 or DNAv than in mice receiving pristane alone. However, when mice previously injected with pristane were inoculated with DNA-hsp65 or DNAv, the protective effect was significantly correlated with lower IL-6 and IL-12 levels and higher IL-10 levels. Our results strongly suggest that DNA-hsp65 has no arthritogenic potential and is actually protective against experimentally induced arthritis in mice.


Subject(s)
Arthritis/prevention & control , Bacterial Proteins/administration & dosage , Chaperonins/administration & dosage , DNA/administration & dosage , Disease Models, Animal , Animals , Chaperonin 60 , Enzyme-Linked Immunosorbent Assay , Interleukin-12/metabolism , Mice
20.
Ann Oncol ; 16(5): 726-34, 2005 May.
Article in English | MEDLINE | ID: mdl-15817602

ABSTRACT

BACKGROUND: The purpose of this study was to assess whether a short course of anthracycline containing chemotherapy followed by high dose therapy with autologous stem-cell support improves disease-free and overall survival as compared with conventional, anthracycline containing chemotherapy, in patients with primary breast cancer and four or more histologically involved lymph nodes. PATIENTS AND METHODS: Two hundred and eighty one patients entered into a randomised clinical trial were allocated to receive standard, conventional treatment (5-fluorouracil, epirubicin and cyclophosphamide-FEC for six cycles) or FEC for three cycles followed by high dose therapy consisting of cyclophosphamide, thiotepa and carboplatin and stem cell rescue (HDT). To be eligible, patients had to be free of overt metastatic disease and be < or =60 years of age. Analyses were according to intention to treat. RESULTS: At a median follow up of 68 months, 118 patients have experienced a relapse or death from breast cancer (62 in the FEC followed by HDT arm and 56 in the conventional FEC arm) and a total of 100 patients have died (54 in the FEC followed by HDT arm and 46 in the conventional FEC arm). No significant difference was observed in relapse-free survival [hazard ratio 1.06, 95% CI 0.74-1.52, p = 0.76] or overall survival [hazard ratio 1.18, 95% CI 0.80-1.75, p = 0.40]. Five patients died from treatment related causes, three as a consequence of HDT and two in the conventional FEC arm. CONCLUSIONS: At the present time, no benefit has been observed from replacing three cycles of conventional chemotherapy with the HDT regimen described here. Patients should continue to receive conventional chemotherapy as adjuvant therapy for breast cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Lymph Nodes/pathology , Neoplasm Recurrence, Local/epidemiology , Stem Cell Transplantation/methods , Adult , Breast Neoplasms/mortality , Chemotherapy, Adjuvant , Combined Modality Therapy , Confidence Intervals , Disease-Free Survival , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , International Cooperation , Mastectomy, Segmental , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Patient Selection , Probability , Prognosis , Proportional Hazards Models , Reference Values , Risk Assessment , Survival Rate , Transplantation, Autologous , Treatment Outcome
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